Kinetochores’ gripping feat: conformational wave or biased diffusion?

Asbury, Charles L.; Tien, Jerry F.; Davis, Trisha N.

doi:10.1016/j.tcb.2010.09.003

Cited by 53 publications

(67 citation statements)

References 82 publications

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“…Previous work in vitro has measured only a small <5 pN force in conjunction with Dam1 and MT disassembly (7,8). Under load, Dam1-coated beads detached frequently from a shortening MT end, raising doubts that Dam1 alone would be a good enough coupler to produce processive chromosome motion or alternatively, that yeast kinetochores ever experience large MT-based forces in vivo (23). Here, we show that Dam1 rings suspended with long heterologous tethers in vitro can withstand loads of up to 30 pN.…”

Section: Discussionmentioning

confidence: 99%

Long tethers provide high-force coupling of the Dam1 ring to shortening microtubules

Volkov¹,

Zaytsev

Gudimchuk

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Microtubule kinetochore attachments are essential for accurate mitosis, but how these force-generating connections move chromosomes remains poorly understood. Processive motion at shortening microtubule ends can be reconstituted in vitro using microbeads conjugated to the budding yeast kinetochore protein Dam1, which forms microtubule-encircling rings. Here, we report that, when Dam1 is linked to a bead cargo by elongated protein tethers, the maximum force transmitted from a disassembling microtubule increases sixfold compared with a short tether. We interpret this significant improvement with a theory that considers the geometry and mechanics of the microtubule-ring-bead system. Our results show the importance of fibrillar links in tethering microtubule ends to cargo: fibrils enable the cargo to align coaxially with the microtubule, thereby increasing the stability of attachment and the mechanical work that it can do. The force-transducing characteristics of fibril-tethered Dam1 are similar to the analogous properties of purified yeast kinetochores, suggesting that a tethered Dam1 ring comprises the main force-bearing unit of the native attachment.laser tweezers | mathematical modeling | microtubule depolymerization | anaphase | forced walk

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Section: Discussionmentioning

confidence: 99%

Long tethers provide high-force coupling of the Dam1 ring to shortening microtubules

Volkov¹,

Zaytsev

Gudimchuk

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Considerable progress in reconstituting the kinetochore-microtubule interface in vitro has provided experimental support for two major coupling models (Asbury et al 2011). The first proposes a biased diffusion mechanism in which the kinetochore contains multiple weak microtubule binding elements that together have enough total energy to maintain an attachment (Hill 1985).…”

Section: Kinetochore-microtubule Attachments and Coupling Activitymentioning

confidence: 99%

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

2013

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The propagation of all organisms depends on the accurate and orderly segregation of chromosomes in mitosis and meiosis. Budding yeast has long served as an outstanding model organism to identify the components and underlying mechanisms that regulate chromosome segregation. This review focuses on the kinetochore, the macromolecular protein complex that assembles on centromeric chromatin and maintains persistent load-bearing attachments to the dynamic tips of spindle microtubules. The kinetochore also serves as a regulatory hub for the spindle checkpoint, ensuring that cell cycle progression is coupled to the achievement of proper microtubule-kinetochore attachments. Progress in understanding the composition and overall architecture of the kinetochore, as well as its properties in making and regulating microtubule attachments and the spindle checkpoint, is discussed. TABLE OF CONTENTS Abstract 817Introduction 818

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“…The current knowledge on the inventory of the mitotic machinery have identified the plausible candidates that give rise to the effectively sleeve-like coupler. The Dam1 ring (also called DASH) and the Ndc80 complex seem to be the strongest candidates for the components of the coupler [16][17][18][19].…”

Section: A Minimal Model: Continuum Formulation and Resultsmentioning

confidence: 99%

Distribution of lifetimes of kinetochore–microtubule attachments: interplay of energy landscape, molecular motors and microtubule (de-)polymerization

Sharma¹,

Shtylla²,

Chowdhury³

2014

Phys. Biol.

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Before a cell divides into two daughter cells, chromosomes are replicated resulting in two sister chromosomes embracing each other. Each sister chromosome is bound to a separate proteinous structure, called kinetochore (kt), that captures the tip of a filamentous protein, called microtubule (MT). Two oppositely oriented MTs pull the two kts attached to two sister chromosomes thereby pulling the two sisters away from each other. Here we theoretically study an even simpler system, namely an isolated kt coupled to a single MT; this system mimics an in-vitro experiment where a single kt-MT attachment is reconstituted using purified extracts from budding yeast. Our models not only account for the experimentally observed "catch-bond-like" behavior of the kt-MT coupling, but also make new predictions on the probability distribution of the lifetimes of the attachments. In principle, our new predictions can be tested by analyzing the data collected in the in-vitro experiments provided the experiment is repeated sufficiently large number of times. Our theory provides a deep insight into the effects of (a) size, (b) energetics, and (c) stochastic kinetics of the kt-MT coupling on the distribution of the lifetimes of these attachments.

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Kinetochores’ gripping feat: conformational wave or biased diffusion?

Cited by 53 publications

References 82 publications

Long tethers provide high-force coupling of the Dam1 ring to shortening microtubules

Long tethers provide high-force coupling of the Dam1 ring to shortening microtubules

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

Distribution of lifetimes of kinetochore–microtubule attachments: interplay of energy landscape, molecular motors and microtubule (de-)polymerization

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